Although the etiology of Alzheimer's Disease (AD) is unknown, a decline in mental health and onset of dementia are clinical hallmarks of the disease. In this study we propose to evaluate in detail, in a longitudinal fashion, the behavioral, cognitive and psychiatric deficits of a well-defined clinical population of AD and control patients who will be followed to autopsy. Our approach bridges the gap between more psychometric measures of deficits and problems of everyday functioning encountered by the patient. As AD is a cellular disease of the CNS we shall use tissue obtained at autopsy to correlate cellular and molecular changes with the clinical data. Recent studies have defined subsets of neurons selectively vulnerable in AD. With tissue from these AD 'target' sites we shall use a new approach to AD, applying monoclonal antibody technology as an analytic tool to define the antigenic and biochemical profile of AD vulnerable cells. Our large panel of 69 antibodies reactive with human CNS tissue, including AD 'target' cells are available for this study. AD 'target' cells will also be examined for AD and aging changes in receptors, and neurotransmitters including those of cholinergic function. With these quantitative methods we plan to link cellular changes to clinically significant events, and verify their importance to the clinical syndrome of dementia. Such information would be invaluable in providing new markers in the diagnosis and psychiatric management of the patient, and contribute to the understanding of the etiology of AD.